Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium
Summary: The serine/arginine-rich (SR) family of splicing factors plays important roles in mRNA splicing activation, repression, export, stabilization, and translation. SR-splicing factor 5 (SRSF5) is a glucose-inducible protein that promotes tumor cell growth. However, the functional role of SRSF5...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-10-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221010658 |
| _version_ | 1818728333958971392 |
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| author | Xiaoli Zhang Ze Wang Qing Xu Yuhan Chen Wen Liu Tong Zhong Hongchang Li Chengshi Quan Lingqiang Zhang Chun-Ping Cui |
| author_facet | Xiaoli Zhang Ze Wang Qing Xu Yuhan Chen Wen Liu Tong Zhong Hongchang Li Chengshi Quan Lingqiang Zhang Chun-Ping Cui |
| author_sort | Xiaoli Zhang |
| collection | DOAJ |
| description | Summary: The serine/arginine-rich (SR) family of splicing factors plays important roles in mRNA splicing activation, repression, export, stabilization, and translation. SR-splicing factor 5 (SRSF5) is a glucose-inducible protein that promotes tumor cell growth. However, the functional role of SRSF5 in tissue development and disease remains unknown. Here, Srsf5 knockout (Srsf5−/−) mice were generated using CRISPR-Cas9. Mutant mice were perinatally lethal and exhibited cardiac dysfunction with noncompaction of the ventricular myocardium. The left ventricular internal diameter and volume were increased in Srsf5−/− mice during systole. Null mice had abnormal electrocardiogram patterns, indicative of a light atrioventricular block. Mechanistically, Srsf5 promoted the alternative splicing of Myom1 (myomesin-1), a protein that crosslinks myosin filaments to the sarcomeric M-line. The switch between embryonic and adult isoforms of Myom1 could not be completed in Srsf5-deficient heart. These findings indicate that Srsf5-regulated alternative splicing plays a critical role during heart development. |
| first_indexed | 2024-12-17T22:28:20Z |
| format | Article |
| id | doaj.art-4e7296b750de47f38845358d009653ee |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-17T22:28:20Z |
| publishDate | 2021-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-4e7296b750de47f38845358d009653ee2022-12-21T21:30:17ZengElsevieriScience2589-00422021-10-012410103097Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardiumXiaoli Zhang0Ze Wang1Qing Xu2Yuhan Chen3Wen Liu4Tong Zhong5Hongchang Li6Chengshi Quan7Lingqiang Zhang8Chun-Ping Cui9The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, 126 Xinmin Avenue, Changchun, Jilin 130021, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, 27 Taiping Road, Beijing 100850, ChinaState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, 27 Taiping Road, Beijing 100850, ChinaCore Facilities Centre, Capital Medical University, Beijing 100069, ChinaState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, 27 Taiping Road, Beijing 100850, ChinaState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, 27 Taiping Road, Beijing 100850, ChinaState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, 27 Taiping Road, Beijing 100850, ChinaState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, 27 Taiping Road, Beijing 100850, ChinaThe Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, 126 Xinmin Avenue, Changchun, Jilin 130021, China; Corresponding authorState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, 27 Taiping Road, Beijing 100850, China; Corresponding authorState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, 27 Taiping Road, Beijing 100850, China; Corresponding authorSummary: The serine/arginine-rich (SR) family of splicing factors plays important roles in mRNA splicing activation, repression, export, stabilization, and translation. SR-splicing factor 5 (SRSF5) is a glucose-inducible protein that promotes tumor cell growth. However, the functional role of SRSF5 in tissue development and disease remains unknown. Here, Srsf5 knockout (Srsf5−/−) mice were generated using CRISPR-Cas9. Mutant mice were perinatally lethal and exhibited cardiac dysfunction with noncompaction of the ventricular myocardium. The left ventricular internal diameter and volume were increased in Srsf5−/− mice during systole. Null mice had abnormal electrocardiogram patterns, indicative of a light atrioventricular block. Mechanistically, Srsf5 promoted the alternative splicing of Myom1 (myomesin-1), a protein that crosslinks myosin filaments to the sarcomeric M-line. The switch between embryonic and adult isoforms of Myom1 could not be completed in Srsf5-deficient heart. These findings indicate that Srsf5-regulated alternative splicing plays a critical role during heart development.http://www.sciencedirect.com/science/article/pii/S2589004221010658Molecular physiologyMolecular biologyMolecular mechanism of gene regulationTranscriptomics |
| spellingShingle | Xiaoli Zhang Ze Wang Qing Xu Yuhan Chen Wen Liu Tong Zhong Hongchang Li Chengshi Quan Lingqiang Zhang Chun-Ping Cui Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium iScience Molecular physiology Molecular biology Molecular mechanism of gene regulation Transcriptomics |
| title | Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium |
| title_full | Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium |
| title_fullStr | Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium |
| title_full_unstemmed | Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium |
| title_short | Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium |
| title_sort | splicing factor srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium |
| topic | Molecular physiology Molecular biology Molecular mechanism of gene regulation Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221010658 |
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